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Fluorescence-based Measurement of Store-operated Calcium Entry in Live Cells: from Cultured Cancer Cell to Skeletal Muscle Fiber
Published on: February 13, 2012
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Store-operated Ca²⁺-entry and adenylyl cyclase
1Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, United Kingdom.
Cell Calcium
|May 17, 2015
Summary
Store-operated calcium entry (SOCE) selectively regulates calcium-sensitive adenylyl cyclase (AC) activity. The source of calcium, not the rise magnitude, determines AC responsiveness, with the molecular basis for AC8 now resolved.
Area of Science:
- Cellular biology
- Molecular signaling
- Calcium signaling
Background:
- Store-operated calcium entry (SOCE) is a critical calcium influx pathway.
- SOCE selectively regulates calcium-sensitive adenylyl cyclase (AC) activity in non-excitable cells.
- The precise mechanism linking SOCE to AC activity has been a long-standing question.
Purpose of the Study:
- To elucidate the molecular basis for SOCE-dependent regulation of adenylyl cyclase 8 (AC8).
- To investigate the role of calcium signaling microdomains centered on ACs.
- To highlight the under-studied physiological relevance of SOCE regulation of ACs.
Main Methods:
- Utilized calcium and cAMP sensors targeted to adenylyl cyclases.
- Investigated the differential contribution of calcium source versus magnitude to AC responsiveness.
- Focused on adenylyl cyclase 8 (AC8) as a model system.
Main Results:
- Demonstrated that the source of calcium influx (SOCE) confers adenylyl cyclase responsiveness, not the magnitude of the calcium rise.
- Resolved the molecular basis for SOCE-dependent regulation of AC8.
- Characterized signaling microdomains associated with ACs using targeted sensors.
Conclusions:
- The molecular basis for SOCE's selective regulation of AC8 activity is now understood.
- Signaling microdomains around ACs play a crucial role in mediating SOCE effects.
- Further research is needed to explore the broader physiological implications of SOCE regulation of ACs.
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